Objective:To study the immunotherapeutic effect of chimeric hepatitis B core protein virus-like particles in subcutaneous lung adenocarcinoma mouse model, lays the foundation for the progression of tumor nano-therapeutic technology development.Methods:The plasmid was constructed by inserting a B-cell epitope of the human epidermal growth factor receptor-2 (HER-2) at hepatitis B core protein′s major immunodominant region (MIR). The recombinant virus nanoparticle, denoted as HBc-HER2, was obtained by E. coli expression system, followed by a series of purification steps. The immune response to this recombinant protein nanoparticle was assessed by measuring levels of anti-HER-2 antibody levels and characterizing antibody isotypes in a subcutaneous tumor mice model of lung adenocarcinoma. While tumor therapeutic efficacy was evaluated by measuring tumor size changes with an electronic caliper and MRI photography of subcutaneous tumor in mice.Results:A high-purity HBc-HER2 recombinant protein was obtained and could assemble into nanoparticle. Animal studies had demonstrated the robust immunogenicity of this vaccine in inducing high levels of HER-2 specific antibodies, yielding positive therapeutic outcomes against tumors.Conclusions:The engineered HBc-HER2 demonstrated notable tumor therapy efficacy in a subcutaneous lung adenocarcinoma mouse model, offering a foundation for tumor therapeutic nanotechnology vaccine research.